Hypercholesterolaemia-induced oxidative stress at the blood-brain barrier


Blood cholesterol levels are not consistently elevated in subjectswith age-related cognitive decline, although epidemiological studies suggest that Alzheimer's disease and cardiovascular diseases share common risk factors. These include the presence of an unusual genetic variant, the APOE4 (apolipoprotein E4) allele, which modulates LDL (low-density lipoproteins) metabolism, increases free radical formation and reduces plasma antioxidant concentrations. Together, these risk factors support a mechanism for increased LDL circulation time and free radical modification of LDL. Plasma oxycholesterols, hydroxylated metabolites of cholesterol, are carried by oxidized LDL, and elevated lipids in mid-life are associated with increased longterm risk of dementia. Although brain cholesterol metabolism is segregated from the systemic circulation, during oxidative stress, plasma oxycholesterols could have damaging effects on BBB (blood-brain barrier) function and consequently on neuronal cells. Cholesterol-lowering drugs such as statins may prevent the modifications to LDL in mid-life and might show beneficial effects in later life. © The Authors Journal compilation © 2014 Biochemical Society.

Publication DOI: https://doi.org/10.1042/BST20140164
Divisions: College of Health & Life Sciences
College of Health & Life Sciences > Chronic and Communicable Conditions
College of Health & Life Sciences > School of Psychology
College of Health & Life Sciences > School of Biosciences > Cell & Tissue Biomedical Research
Additional Information: © the Biochemical Society. Provided the original publication of the article, or portion of the article, is properly cited, Authors retain the following non-exclusive rights: 1.To reproduce their article in whole or in part in any printed volume (book or thesis) of which they are the Author or Editor 2.To reproduce their article in whole or in part at the Author's current academic institution for teaching purposes 3.To reuse figures, tables, illustrations or photos from the article in commercial or non-commercial works created by them 4.To post a copy of the Immediate Publication (i.e. the Accepted Manuscript*) at the Author's Institutional Repository, 6 months after publication, provided that this is linked to the article on the journal website (e.g. through the DOI).
Uncontrolled Keywords: alzheimer's disease,blood-brain barrier,liver X receptor (LXR),low-density lipoprotein (LDL),oxidative stress,oxysterol,statin,Biochemistry
Publication ISSN: 1470-8752
Last Modified: 17 May 2024 07:11
Date Deposited: 19 Aug 2014 13:35
Full Text Link: http://www.bioc ... /bst0421001.htm
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2014-08
Authors: Dias, Irundika H.K. (ORCID Profile 0000-0002-6620-8221)
Polidori, Maria C.
Griffiths, Helen R. (ORCID Profile 0000-0002-2666-2147)



Version: Accepted Version

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